Nondriver NSCLC: Frontline Systemic Therapy

Benjamin P. Levy, MD, explains the factors to consider when deciding on a treatment approach in the frontline setting of advanced nondriver non–small cell lung cancer and the use of immunotherapy/chemotherapy combinations.

Benjamin P. Levy: For patients who don’t have an actionable mutation but have advanced lung cancer, I think these patients obviously warrant systemic chemotherapy, and chemotherapy remains the standard of care for these patients. At least in my mind, chemotherapy selection is still histology directed. For patients who have advanced adenocarcinoma, I think pemetrexed-based regimens with carboplatin are still considered the standard. For patients with squamous cell carcinoma, I think we have competing standards. I’ve been more on the carboplatin/Abraxane [paclitaxel albumin-bound] front. I use that regimen more commonly than potentially carboplatin/paclitaxel or carboplatin/gemcitabine. So, I think first and foremost, we have to look at the histology of patients.

Secondly, you have to look at the patient’s performance status to see and understand whether or not they can tolerate a platinum doublet, and then you also have to understand what the patient’s goals are. I think we need to realize that these patients come in and, unfortunately, chemotherapy can’t cure them. It can extend their life, and it’s important. It can make them feel better. But I think we need to understand what the patient’s long-term goals are. I would say looking at the histology is important in selecting chemotherapy for those patients who don’t have a driver mutation. Obviously, if PD-L1 is negative, they’re not going to get immunotherapy. I think we’re going to talk a little bit about the role of adding immunotherapy to platinum chemotherapy up front. But I think with histology, patient performance, tumor burden, and symptoms, all of this needs to be factored in when making a treatment decision for a treatment-naive patient.

In my mind, this is very controversial. We have a phase II trial that has been published of roughly 120 patients who had advanced stage lung cancer with all PD-L1 levels. It didn’t matter what your PD-L1 was. There was no cutoff point. They were randomized to either carboplatin/pemetrexed or carboplatin/pemetrexed with pembrolizumab. They were asking a question: Can we add immunotherapy to chemotherapy in a nonselect way and improve outcomes? And that trial showed a benefit in response rate, it showed a benefit in progression-free survival, but it showed no benefit in overall survival. We have a phase III trial that is already completed with the same design, KEYNOTE-189, in which we’ll have better answers from a larger trial.

I would say I’m not using immunotherapy, pembrolizumab, with chemotherapy yet. I think there are select patient populations in which we can consider it, perhaps in patients with a tumor proportion score of less than 50%, but in the 30% to 50% range in which we’re trying to elicit a response. Maybe that’s an ideal candidate. But, for the most part, I haven’t been using it yet, and I think the data will tell us more. The phase III trial will hopefully be reported next year in the second quarter of 2018, and we’ll have a better answer to if immunotherapy added to chemotherapy actually extends survival. That’s what’s important for me. So, as of now, in select cases I use it; but, for the most part, I’m still sticking with just a chemotherapy backbone.